Liu Wei-Ting, Lee Wen-Bin, Tsai Yi-Cheng, Chuang Yuan-Jhe, Hsu Keng-Fu, Lee Gwo-Bin
Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, Tainan 70403, Taiwan.
Biomicrofluidics. 2019 Feb 25;13(1):014114. doi: 10.1063/1.5085133. eCollection 2019 Jan.
Because of the difficulty of treatment in its latest stages, cancer is among the leading causes of death worldwide. Therefore, high-affinity and specificity biomarkers are still in demand for many cancer types, and the utility of aptamers to serve in this regard has been explored recently. Although a process known as "systematic evolution of ligands by exponential enrichment" (SELEX) has been used to generate aptamer-based cancer biomarkers, this approach is complicated, time-consuming, and labor-intensive. An automated microfluidic system was consequently developed herein to screen ovarian cancer-specific aptamers via on-chip SELEX with clinical cancer tissue samples. The integrated microfluidic system consisted of an integrated microfluidic chip, a temperature control module equipped with 12 thermoelectric coolers, and a flow control module for controlling 36 electromagnetic valves such that the entire, tissue-based SELEX process could be fully automated and carried out within 15 h. Highly specific ovarian cancer aptamers with high affinity (dissociation constant of 129 nM) to their cellular targets were screened with this system. Given the comparable specificity to their much more expensive antibody counterparts, these aptamers, when used in conjunction with the developed microfluidic system, may be used to diagnose ovarian cancer in its earliest stages.
由于癌症在其晚期治疗困难，它是全球主要死因之一。因此，许多癌症类型仍需要高亲和力和特异性的生物标志物，最近人们探索了适体在这方面的应用。尽管一种称为“指数富集配体系统进化”（SELEX）的方法已被用于生成基于适体的癌症生物标志物，但这种方法复杂、耗时且 labor-intensive。因此，本文开发了一种自动化微流控系统，通过与临床癌症组织样本进行芯片上的SELEX来筛选卵巢癌特异性适体。该集成微流控系统由一个集成微流控芯片、一个配备12个热电冷却器的温度控制模块和一个用于控制36个电磁阀的流量控制模块组成，以便整个基于组织的SELEX过程能够完全自动化并在15小时内完成。用该系统筛选出了对其细胞靶点具有高亲和力（解离常数为129 nM）的高度特异性卵巢癌适体。鉴于其与昂贵得多的抗体相当的特异性，这些适体与开发的微流控系统结合使用时，可用于在卵巢癌的最早阶段进行诊断。
